We and others have demonstrated limitation in coronary flow reserve of the coronary micro-circulation to be a frequent mechanism of angina pectoris in patients with angiographically normal epicardial coronary arteries. We have found that this limited flow reserve can be demonstrated during rapid atrial pacing, especially after ergonovine administration, associated with angina pectoris and metabolic and hemodsynamic evidence of myocardial ischemia. Because pacing does not allow assessment of total transmural coronary flow reserve, a potent coronary arterial vasodilator (dipyridamole) was utilized to investigate peak flow reserve in patients with anginal pain despite normal epicardial coronary arteries. Twenty patients were identified as having abnormal vasodilator reserve on the basis of precipitation of typical chest pain after pacing following the administration of ergonovine. Compared to 11 patients without chest pain, these 20 patients had significantly lower coronary blood flow and higher calculated coronary resistance during pacing after ergonovine. After administration of dipyridamole, the same 20 patients had significantly less of an increase in transmural coronary flow compared to the patients with normal flow reserve based on the pacing study after ergonovine. Additionally, 13 of the 20 patients experienced severe chest pain during dipyridamole despite an increse in flow. Only one control patient experienced chest pain. Thus patients with impaired coronary flow reserve in response to increasing myocardial oxygen demands also have limitation of flow reserve in response to dipyridamole, suggesting that maximal vasodialtor reserve is reduced. This is compatible with the concept of a coronary myocardial redistribution of coronary flow away from the endocardium to the epicardium because of narrowing of small prearteriolar coronary arteries.